EP0559249B1 - Method of testing aqueous samples for water treatment polymers - Google Patents
Method of testing aqueous samples for water treatment polymers Download PDFInfo
- Publication number
- EP0559249B1 EP0559249B1 EP93200270A EP93200270A EP0559249B1 EP 0559249 B1 EP0559249 B1 EP 0559249B1 EP 93200270 A EP93200270 A EP 93200270A EP 93200270 A EP93200270 A EP 93200270A EP 0559249 B1 EP0559249 B1 EP 0559249B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- water treatment
- copolymer
- acid
- polymer
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
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- 238000010998 test method Methods 0.000 title 1
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- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5308—Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2430/00—Assays, e.g. immunoassays or enzyme assays, involving synthetic organic compounds as analytes
- G01N2430/60—Synthetic polymers other than synthetic polypeptides as analytes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/815—Test for named compound or class of compounds
Definitions
- the present invention relates to a determination method, in particular to a method, based on immunoassay, for the determination of water treatment chemicals in aqueous media, and to novel antibodies and hybridomas useful in the new method.
- dissolved salts of metals such as calcium, magnesium, barium and strontium.
- the dissolved salts may be converted to insoluble salts, and thereupon deposited as scale on any heat transfer surfaces in contact with the water or aqueous system.
- Insoluble salt scale may be formed even when the water or aqueous system is merely concentrated, without being heated.
- Such precipitation and scale deposition are troublesome and can result in an increase in the costs required to maintain aqueous systems in good working order.
- problems caused by scale deposits are obstruction of fluid flow, impedance of heat transfer, wear of metal parts, shortening of equipment life, localised corrosion attack, poor corrosion inhibitor performance and unscheduled equipment shutdown.
- problems can arise, e.g. in any circulating water system such as those used in oil drilling wells, steam power plants, water desalination plants, reverse osmosis equipment, heat exchange equipment and equipment concerned with the transport of products and by-products in aqueous media, e.g. fly-ash formed during the combustion of coal, in the production of electricity.
- a number of additives notably polycarboxylates, have been provided as effective scale inhibitors for addition to aqueous systems.
- colorimetric methods are available for the determination of scale inhibitors, e.g. polycarboxylates.
- Colorimetric methods have the disadvantage that they are subject to interference from extraneous materials. In oil field applications, for instance, interference arises mainly from iron and oil-derived organic materials.
- a sample-preparation (pretreatment) cartridge maybe employed, in which interfering species are removed and the water treatment chemical is concentrated.
- pretreatment water treatment chemical
- Such techniques can result in loss of the water treatment chemical being determined due to competition from the organics for adsorption sites on the cartridge.
- Such methods are time consuming, lack robustness and the required sensitivity (limits of detection only 1-2 ppm).
- they require a certain amount of expertise in order to be used effectively to conduct the required determination.
- Immunological methods for determining proteins, cells, hormones, vitamins, drugs and mycotoxins etc. have been known for many years, and have been widely reported in the literature.
- an animal often a mouse or rabbit, is immunized, either with an analyte or a protein-analyte conjugate.
- the antibodies produced by the animal are then used, in the form of an immunoassay, to determine the analyte. These methods are based upon the specific reaction between the analyte and the antibody.
- EP 540 314 and EP 535 347 which were published after the filing date of the present application, relate to methods of making or using monoclonal antibodies specific for polyacrylate copolymers.
- the present invention provides methods for determining the presence and/or concentration of a water treatment polymer in an aqueous sample; compositions for use in such methods; and methods of making antibodies and hybridomas which secrete monoclonal antibodies; the invention being defined by the accompanying set of claims.
- R" is hydrogen, methyl or ethyl
- R is hydrogen, C 1 -C 18 alkyl, C 5 -C 12 cycloalkyl, aryl, aralkyl, a residue of formula: in which R" has its previous significance and the sum of m and n is an integer of at most 100, or R is a residue -OX in which X is hydrogen or C 1 -C 4 alkyl, and R 1 is a residue -OX in which X has its previous significance.
- telomers of formula I are those having the formula IA: in which the sum of m' and n' is an integer ranging from 4 to 32, especially, 15 to 20.
- terpolymers of maleic anhydride with other monomers the molar ratio of maleic anhydride to the other monomers ranging from 2.5:1 to 100:1 and the molecular weight of the terpolymer being below 1000.
- Such terpolymers are described in US 4126549.
- Preferred ratios of monomers in the terpolymer are in the range of 24-34:1 of maleic anhydride to other monomers.
- Preferred other monomers are vinyl acetate acid and ethyl acrylate.
- ratios are those used in the preparation of the cotelomer of formula II and are not necessarily the ratios to be found in the final cotelomer.
- preferred water treatment molecules include other polyacrylic acid polymers; copolymers of acrylic acid and acrylamidomethylpropane sulphonic acid (AMPS); copolymers of acrylic acid and vinyl acetate; polymaleic acid; hydrolysed polymaleic acid; terpolymers of maleic acid, ethyl acrylate and vinyl acetate; copolymers of acrylic acid and maleic anhydride; copolymers of maleic acid and sodium allyl sulphonate; and copolymers of maleic anhydride and sulphonated styrene and vinyl sulphonic acid telomers.
- AMPS acrylamidomethylpropane sulphonic acid
- aqueous systems in which water treatment polymers to be determined may be present, of particular interest are the aqueous systems employed in cooling water plant steam generating plant, sea-water evaporators, reverse osmosis equipment, paper manufacturing equipment, sugar evaporator equipment, soil irrigation plant, hydrostatic cookers, gas scrubbing systems, closed circuit heating systems, aqueous-based refrigeration systems and down-well systems.
- the antibody used in the method and composition of the present invention may be produced by known techniques.
- an immunogenic conjugate of the polymer and a macromolecule carrier may be produced; an animal may then be immunized with the conjugate, the polymer alone, adjuvant or a discrete mixture of each; blood may be removed from the animal and the serum separated from the blood; and finally the polyclonal antibodies may be recovered from the serum.
- Monoclonal antibodies which are reactive with specific epitopes on the water treatment polymer, in the method and composition of the present invention, especially in view of their superior specificity for a particular polymer.
- Monoclonal antibodies may be obtained by the technique first described by Kohler and Milstein, Nature, 265:495 (1975). This technique comprises providing an immunogenic form of the specific water treatment polymer; immunizing an animal with such; obtaining antibody-producing cells from the animal; fusing the cells so obtained with myeloma cells to produce hybridomas; selecting from the hybridomas a hybridoma which produces an antibody which reacts with the specific water treatment polymer; and then isolating the monoclonal antibody from the selected hybridoma.
- Water treatment polymers generally have low molecular weights and do not, per se, induce the production of antibodies. They can be used as a hapten, however, in combination with a higher molecular weight, immunogenic carrier, such as a protein, using e.g. the technique disclosed by Albro et al. Toxicol Appl. Pharmacol 50, 137-146 (1979).
- the conjugate so obtained may then be used to immunize an animal host, by conventional techniques, e.g. inoculation.
- the animal host may be, e.g. a rabbit or a rodent such as a rat or mouse.
- polyclonal antibodies may be recovered from the animal by conventional techniques.
- blood may be removed from the animal and serum may be separated from the blood so removed.
- the desired antibodies may then be removed from the serum, e.g. by affinity purification or salt fractionation.
- cells which produce antibodies may be recovered from the immunized animal.
- B lymphocytes removed from the animal's spleen are preferred.
- the removed cells are fused with myeloma cells to produce hybridomas, which are then separated, again using standard techniques such as cloning by limiting dilution.
- hybridomas Once the hybridomas have been separated a selection is made to ascertain those which produce antibodies to the specific water treatment polymer to be determined in the method of the present invention.
- the relevant specific hybridomas can then be isolated by known methods, and the relevant antibodies secreted from them by conventional techniques.
- telomer 1 derived from 16 moles of acrylic acid and 1 mole of hypophosphorous acid and produced by the method of US 4046707 is bound to a carrier protein keyhole limpet haemocyanin (KLH) using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC).
- EDC 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride
- OVA ovalbumin
- the 500 ⁇ l of peptide solution are added to the 200 ⁇ l of carrier protein solution.
- this solution is added to 10mg of EDC and dissolved by gentle mixing.
- the 10mg of EDC are dissolved in 1 ml of deionized water and 50 ⁇ l of this solution are added immediately to the carrier - peptide solution.
- the reaction proceeds for 2 hours at room temperature. Any precipitate is removed using centrifugation prior to purification.
- the conjugate is purified using gel filtration or Sephadex® G50 (0.5 x 5 cm).
- the column is washed using 5ml of phosphate buffered saline PBS.
- the peptide carrier mixture is applied directly to the top of the column and the eluate collected.
- 0.5ml aliquots of PBS are added and each fraction is collected in a separate tube.
- 15mls of PBS are added to elute both the conjugate and the peptide.
- the immunogen elutes between fractions 4-6, and the free peptide and reagents after fraction 8.
- the hapten - carrier ratios are determined spectrophotometically and by assessment of the concentrations of the reactants following conjugation.
- the molar ratio of polymer per 100,000 mol. wt of carrier is 6-11.
- mice immunised as indicated above, are injected with polymer or conjugate (at the doses shown in 2a) 3 days prior to sacrifice.
- the spleens are removed and the splenocytes isolated by dissection into Hanks Balanced Salt Solution. These spleen cells are fused with cells from the X63.Ag 8 6.5.3 murine myeloma line, in exponential growth, in a ratio of 4:1 by the addition of 1 ml 46% (w/v) polyethylene glycol 1550 (Serva) in RPMI 1640 with gentle mixing for 3 min at 37°C. After standing for 2 min at room temperature, the mixture is slowly diluted by the drop-wise addition of 20ml RPMI 1640 over 5 min, followed by standing at room temperature for 10 min.
- Serva polyethylene glycol 1550
- the cells After washing twice with RPMI 1640, the cells are incubated for 2 hr at 37°C in bicarbonate-buffered RPMI 1640, supplemented with 10% (v/v) fetal calf serum, 2mmol/l L-glutamine, 50 IU/ml penicillin and 50 ⁇ g/ml streptomycin (Flow) and containing 1 x 10 -4 mol/l hypoxanthine and 1.6 x 10 -5 mol/l thymidine (HT medium).
- the cell suspensions (100 ⁇ l) are then dispensed into 96-well tissue culture plates (Costar) at three different concentrations (2.5, 1.25 and 6 x 10 6 cells/ml).
- HAT medium 200 ⁇ l HT medium containing 4 x 10 -7 mol/l aminopterin (HAT medium) are added to each well.
- the plates are incubated at 37°C in a humidified atmosphere of 5% CO 2 in air.
- Hybridoma cells are initially grown in HAT medium but this is eliminated after 14 days by step-wise replacement with HT medium.
- Supernatant liquids are screened for specific antibody by indirect non-competitive ELISA 14-18 d post-fusion. Specific hybridomas are subsequently expanded into flasks and cloned three times or until 100% cloning efficiency is obtained.
- This procedure is carried out by limiting dilutions in 96-well tissue culture plates containing a feeder layer of spleen cells (2 x 10 5 cells/well) from non-immunized NZB/DALB-C hybrid mice.
- Cell lines of interest are maintained in vitro in culture medium and are frozen, at a concentration of 5 x 10 6 cells/ml, in RPMI 1640 containing 30% bovine serum and 15% dimethyl sulphoxide (Sigma) and stored in liquid nitrogen (Islam, M.S. and Stimson, W.H. Lett. Appld. Microbiol., 4, 85-89 (1987).
- Assays incorporating polyclonal or monoclonal antibodies to the conjugated form are sensitive only down to 10 ⁇ g/ml. Those incorporating polyclonal and monoclonal antibodies to the free form are sensitive down to 0.1 ⁇ g/ml (c.f. Figure 1).
- the product is prepared in a variety of synthetic waters and two examples of typical north sea formation water in which the product is commonly applied, to determine matrix interference (see Table 1).
- Absorbance (A450) of the positive polymer control in the presence of distilled water is 1.68 ⁇ 0.19 AU.
- A450 of the negative polymer control is 0.08 ⁇ 0.04 AU.
- A450 in the presence of the synthetic waters and one of the north sea formation waters was > 1.58 ⁇ 0.28 AU.
- the second formation water brought about a colour change when added to the tetramethylbenzidine substrate.
- TYPE COMPOSITION FORMATION 1 Barium (Ba 2+ ) 1050 ppm Calcium (Ca 2+ ) 1060 ppm Magnesium (Mg 2+ ) 113 ppm Sodium (Na + ) 27,986 ppm Chloride (Cl - ) 43,196 ppm Potassium (K + ) 3833 ppm Strontium (Sr 2+ ) 110 ppm SEAWATER 1 Sulphate (SO 4 2- ) 2426 ppm Sodium (Na 2- ) 22,135 ppm Chloride (Cl - ) 34,165 ppm Potassium (K + ) 775 ppm Bicarbonate (HCO 3 - ) 497 ppm THESE ARE MIXED 50/50 or 40/60 OF FORMATION 1/SEAWATER 1 and pH adjusted to 4.5 FORMATION 2 Barium (Ba 2+ ) 252 ppm Calcium (Ca 2+ ) 3523 ppm Magnesium
- Example 1 Mice and rabbits are immunised as described in Example 1. Antibody production is determined after immobilisation of the second BSA-conjugate onto the walls of a microtitration well and the procedure described in Example 1 is performed.
- the conjugated form of the product is shown to be immunogenic. No response is detected from the free form. This is consistent with the size of the molecule being too small (mw ⁇ 1000 daltons) to stimulate the immune system.
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- Food Science & Technology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB929204409A GB9204409D0 (en) | 1992-02-29 | 1992-02-29 | Determination method |
GB9204409 | 1992-02-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0559249A1 EP0559249A1 (en) | 1993-09-08 |
EP0559249B1 true EP0559249B1 (en) | 2002-06-26 |
Family
ID=10711299
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP93200270A Expired - Lifetime EP0559249B1 (en) | 1992-02-29 | 1993-02-03 | Method of testing aqueous samples for water treatment polymers |
Country Status (14)
Country | Link |
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US (3) | US6146903A (ja) |
EP (1) | EP0559249B1 (ja) |
JP (1) | JPH0820445B2 (ja) |
AU (1) | AU662388B2 (ja) |
BR (1) | BR9300651A (ja) |
CA (1) | CA2089395C (ja) |
DE (1) | DE69332052T2 (ja) |
ES (1) | ES2179048T3 (ja) |
GB (1) | GB9204409D0 (ja) |
MX (1) | MX9300911A (ja) |
NO (1) | NO930705L (ja) |
PT (1) | PT559249E (ja) |
TW (1) | TW345616B (ja) |
ZA (1) | ZA93782B (ja) |
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US5593850A (en) * | 1991-08-30 | 1997-01-14 | Nalco Chemical Company | Monitoring of industrial water quality using monoclonal antibodies to polymers |
GB9204409D0 (en) * | 1992-02-29 | 1992-04-15 | Ciba Geigy Ag | Determination method |
US5834215A (en) * | 1994-10-05 | 1998-11-10 | The Administrators Of The Tulane Educational Fund | Method for detecting antipolymer antibodies and diagnosing silicone related disease (SRD) fibromyalgia and chronic fatigue syndrome (CFS) |
ZA97248B (en) | 1996-01-18 | 1997-07-18 | Rohm & Haas | Method for identifying and quantifying polymers utilizing immunoassay techniques |
US6096563A (en) * | 1996-03-29 | 2000-08-01 | Strategic Diagnostics Inc. | Dual particle immunoassay method and kit |
US8449842B2 (en) * | 2009-03-19 | 2013-05-28 | Thermo Scientific Portable Analytical Instruments Inc. | Molecular reader |
AU2010240531B2 (en) * | 2009-04-21 | 2016-02-04 | Ecolab Usa Inc. | Catalytic water treatment method and apparatus |
BR112013013856A2 (pt) | 2010-12-21 | 2016-09-13 | Gen Electric | métodos para detectar polímero catiônico |
US9193610B2 (en) | 2011-08-10 | 2015-11-24 | Ecolab USA, Inc. | Synergistic interaction of weak cation exchange resin and magnesium oxide |
US11090606B2 (en) | 2013-12-05 | 2021-08-17 | Dionex Corporation | Gas-less electrolytic device and method |
FI127399B (en) | 2016-02-19 | 2018-05-15 | Kemira Oyj | A method for treating a liquid sample |
US10900959B2 (en) | 2018-06-14 | 2021-01-26 | S.P.C.M. Sa | Method for quantitatively measuring the concentration of chemicals in aqueous solution |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
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US4126549A (en) * | 1973-02-14 | 1978-11-21 | Ciba-Geigy (Uk) Limited | Treatment of water |
GB1414918A (en) * | 1973-02-14 | 1975-11-19 | Ciba Geigy Uk Ltd | Treatment of water to prevent the deposition of scale |
GB1458235A (en) * | 1974-06-11 | 1976-12-08 | Ciba Geigy Uk Ltd | Inhibiting scale formation in aqueous systems |
DE2525859C2 (de) * | 1974-06-11 | 1983-03-03 | Ciba-Geigy (Uk) Ltd., London | Verfahren zur Behandlung von wäßrigen Systemen |
JPS6041008B2 (ja) * | 1977-08-09 | 1985-09-13 | 日本酸素株式会社 | ガラス等の溶融方法 |
GB8401166D0 (en) * | 1984-01-17 | 1984-02-22 | Bevaloid Ltd | Labelled polymer compositions |
US4959457A (en) * | 1984-05-31 | 1990-09-25 | Genentech, Inc. | Anti-lymphotoxin |
US4752443A (en) | 1986-05-09 | 1988-06-21 | Nalco Chemical Company | Cooling water corrosion inhibition method |
US4756881A (en) | 1986-05-09 | 1988-07-12 | Nalco Chemical Company | Composition of corrosion inhibitors for cooling water systems using chemically modified acrylamide or methacrylamide polymers |
IL83419A0 (en) * | 1986-09-15 | 1988-01-31 | Westinghouse Electric Corp | Antibodies reactive with chlorinated phenols,their preparation and their use |
EP0321546A1 (en) * | 1987-06-09 | 1989-06-28 | PECK, Dana P. | Immunoassay for aromatic ring containing compounds |
US5593850A (en) * | 1991-08-30 | 1997-01-14 | Nalco Chemical Company | Monitoring of industrial water quality using monoclonal antibodies to polymers |
CA2075695C (en) * | 1991-08-30 | 2003-05-20 | Robert L. Wetegrove | Monoclonal antibodies to sulfonated polymers |
JPH05260991A (ja) * | 1991-10-31 | 1993-10-12 | Nalco Chem Co | ポリアクリレートポリマーに対するモノクローナル抗体 |
GB9204409D0 (en) * | 1992-02-29 | 1992-04-15 | Ciba Geigy Ag | Determination method |
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- 1992-02-29 GB GB929204409A patent/GB9204409D0/en active Pending
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1993
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- 1993-02-03 PT PT93200270T patent/PT559249E/pt unknown
- 1993-02-03 ES ES93200270T patent/ES2179048T3/es not_active Expired - Lifetime
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- 1993-02-12 CA CA002089395A patent/CA2089395C/en not_active Expired - Lifetime
- 1993-02-19 BR BR9300651A patent/BR9300651A/pt not_active Application Discontinuation
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CA2089395A1 (en) | 1993-08-30 |
CA2089395C (en) | 2001-07-10 |
US6420530B1 (en) | 2002-07-16 |
ZA93782B (en) | 1993-09-08 |
AU662388B2 (en) | 1995-08-31 |
GB9204409D0 (en) | 1992-04-15 |
US6911534B2 (en) | 2005-06-28 |
DE69332052T2 (de) | 2002-12-19 |
BR9300651A (pt) | 1993-08-31 |
NO930705L (no) | 1993-08-30 |
ES2179048T3 (es) | 2003-01-16 |
TW345616B (en) | 1998-11-21 |
MX9300911A (es) | 1994-07-29 |
DE69332052D1 (de) | 2002-08-01 |
PT559249E (pt) | 2002-11-29 |
NO930705D0 (no) | 1993-02-26 |
AU3385693A (en) | 1993-09-09 |
EP0559249A1 (en) | 1993-09-08 |
JPH0678762A (ja) | 1994-03-22 |
JPH0820445B2 (ja) | 1996-03-04 |
US20020127611A1 (en) | 2002-09-12 |
US6146903A (en) | 2000-11-14 |
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